Proposed herein is a program aimed at applying the methods of parallel and combinatorial synthesis, molecular enzymology, and high throughput screening to determining the preferred substrate specific membrane bound antigen (PSMA) and developing lead inhibitors of the proteolytic activity of this protein. These studies will set the stage for a detailed examination of the biological function of PSMA and its potential as a diagnostic or therapeutic target in the treatment of prostate cancer. The project is designed to encourage the interaction of three groups: chemistry and protease groups at UCSF and a chemistry group at SFSU. The interaction of these groups should provide training opportunities to encourage minority students to pursue careers in cancer research and provide students at the Minority institution (SFSU) access to state of the art techniques in chemical biology. Relationship to the Overall Priorities and Objectives of the Partnership between UCSF and SFSU. The interaction of these groups should provide training opportunities of three groups: chemistry and protease groups at UCSF and a chemistry group at SFSU. The interaction of these groups should provide training opportunities to encourage minority students to pursue careers in cancer research and provide students at the Minority institution (SFSU) access to state of the art techniques in chemical biology. Relationship to the Overall Priorities and Objectives of the Partnership between UCSF and SFSU. In 1998, UCSF established a new graduate program in Chemistry and Chemical Biology (CCB). The aim of this predoctoral training program is to foster research that exploits and develops chemical strategies to understand and control fundamental biological processes. The program provides a rich venue for chemical research as it interfaces with biology by bringing together 43 investigators and resources from seven departments at UCSF and UCB. Craik is the director of the program and Guy is a very active member in the synthetic chemistry group. The research in CCB has direct relevance to national priorities in human health and addresses central problems in chemical biology including: molecular recognition, protein folding, signal transduction, protein trafficking, computer aided design, combinatorial synthesis, genomics, proteomics and quantitative approaches to cellular signaling. These studies use model systems ranging from bacteria to humans and encompass technologies including chemical synthesis, combinatorial chemistry crystallography, NMR spectroscopy, mass spectroscopy, and computational modeling. Nine new students will be arriving in September and we expect approximately 12 to 15 students per year at a steady state. The UCSF CCB program provides a unique opportunity to interact with SFSU at the undergraduate and graduate student level. Underrepresented minority candidates are actively sought in an extensive series of programs at UCSF including the Science Education Partnership and the UCSF-based undergraduate Summer Research Training Program (the CCB director, Craik, is a member of both executive committees and Guy an active participant). A non-scientific aim of the UCSF-SFSU program is the recruitment of SFSU students (either MS or BS) into the CCB program. SFSU has a weekly seminar series that is attended by faculty and students (both BS and MS). Craik and Guy have already agreed to speak in these seminar series in order to strengthen the proposed collaboration as well as assist with additional "recruitment" of qualified students. While there has been a recent shift in focus of many traditional chemistry departments to biological problems, the departments often lack strong ties to biologically based research programs. UCSF can be an important link for SFSU to strengthen its own chemical biology research. We believe that UCSF, with its extraordinary interactive research culture and unique mix of basic science and clinical research faculty is a perfect environment in which to carry out research at the interface of chemistry and biology. Located within a major health science campus, faculty in the CCB Program are poised to apply chemical approaches to important problems in human health, particularly cancer, one of the focus areas of the U56 MI/CCP proposal. We feel that the CCB program will provide an exciting environment for learning modern chemical principles and techniques to study significant problems at the interface of chemistry and biology. We hope that the SFSU graduate programs will benefit as CCB enables more chemical research to be carried out in the biochemical areas on both campuses.